What if we could turn off the cause of Huntington’s disease?

What if scientists could simply switch off a mutated gene causing a debilitating neurodegenerative disorder like Huntington’s disease?

Known as gene (or genome) editing, that approach is a current hot research topic, generating hope for sufferers of genetic diseases like HD.

Gene editing will be the focus of a symposium on September 4 sponsored by life science start-up incubator Johnson & Johnson Innovation, JLABS (hereafter simplified as JLABS) and the Janssen Pharmaceutical Companies, the drug-discovery arm of Johnson & Johnson, in San Diego, CA.

At the sponsors’ invitation, I will give a presentation, based on my two decades as an HD advocate, on the health and social challenges faced by HD-affected individuals and their families. The two firms have also invited seven leading scientists and biotech executives to speak at the symposium, titled “Science Alliance: Silencing Neurodegenerative Diseases and Sensory Disorders with Gene Editing.”

HD community members can watch the live webcast of the event for free by registering at the event website and entering the discount code “HDCOMMUNITY” at check out. Attendance in person is $35 for the general public and $20 for students and academics, at the JLABS facility at 3210 Merryfield Row, San Diego.

Recent milestones in gene therapy “have ignited interest” in the field and “especially its application to neurological disorders,” the website states. Gene editing has opened the door to innovation in the treatment of diseases like HD, spinal muscular atrophy, and ALS, according to the organizers.

The website points out that, as the technology progresses, key questions are emerging, such as how to effectively deliver gene editing drugs to the brain.

Owned by Johnson & Johnson, JLABS provides labs, offices, marketing, education, and events for early-stage life-science companies unaffiliated with Johnson & Johnson. In San Diego, one of the world’s leading biotech hubs, it offers services to 60 companies; globally, JLABS serves 580 companies.

The pharmaceutical arm of Johnson & Johnson, the Belgium-based Janssen was acquired in 1961.

Advances in gene editing

Gene editing is different from gene silencing, the technique used in the Phase 3 Roche clinical trial currently in progress in the U.S. and a projected 17 other countries (click here to read more). Roche’s RG6042 is an antisense oligonucleotide, an artificial strand of DNA designed block the production of the huntingtin protein in brain cells.

With gene editing, scientists make changes in the actual DNA – a revolution in biomedical research.

The gene-editing technology currently getting the most attention – one already used in the search for HD treatments – is known as CRISPR. Scientists first observed CRISPR occurring naturally in bacteria in the 1990s. In 2002, scientists discovered additional DNA instructions called “Cas.” The combination CRISPR/Cas actually comprises the bacterial immune system. (Click here to read more.)

“There’s no equivalent of word processing software to edit genes,” then Ph.D. candidate Leora Fox (now a Ph.D.) wrote in HDBuzz in 2017. “To fix genes on a microscopic scale, one cell at a time, the faulty code has to be located and physically cut – and that’s what CRISPR/Cas does.”

To alter a gene, scientists need to insert CRISPR/Cas into the cells.

(Image credit: Ernesto del Aguila III, National Human Genome Research Institute, and Wikimedia Commons)

In a disease like HD, the goal is to use this mechanism to cut directly (that is, shorten) the defective, elongated gene. Researchers are also looking at other ways to deploy gene editing.

In recent years, HD research groups have used this technology to edit the HD gene in the brains of genetically modified “HD mice”. One group developed a technique that led to beneficial effects in mice, including the recovery of older mice that had already developed symptoms. (Click here to read more.)

Chinese researchers have used gene editing in human embryos to fix the mutation behind the blood disease beta-thalassemia, which reduces the amount of red blood cells. However, the embryos were not implanted. 

Gene editing is still far from use in human clinical trials. Among the challenges, scientists need to find ways to effectively deliver such a treatment to the brain and avoid inadvertent editing of other genes. (Click here to read more.)

(Late last year a researcher in China claimed to have used CRISPR to alter the genomes of twin baby girls through in vitro fertilization to enable them to resist potential infection from HIV. The news of this development sparked renewed controversy over the use of biotechnology to intervene in human life.)

The symposium participants

To explore gene editing in neurodegenerative and sensory disorders (difficulties with the five senses), JLABS and Janssen have invited seven researchers and executives to the September 4 symposium, including at least two with experience with CRISPR. They include:

Leah Aluisio, Associate Director, Janssen Research and Development;

Alexis C. Komor, Ph.D., Assistant Professor, Department of Chemistry and Biochemistry, UCSD; 

Young Jik Kwon, Ph.D., Professor, Department of Pharmaceutical Sciences, University of California, Irvine, and co-founder, Responsive Polymers Therapeutics, Inc., and Jupiter Therapeutics, Inc.;

Sanjay Mistry, Ph.D., Head of JLABS @ San Diego, Johnson & Johnson Innovation, JLABS;

Gerry Rodrigues, Associate Vice President, Allergan;

Arthur Suckow, Ph.D., CEO, DTx Pharma; and

Gene Yeo, Ph.D., MBA, Professor, University of California, San Diego, and co-founder, Locana and Eclipse Bioinnovations.

Their bios are available on the event website.

Imagining a cure?

As a speaker, I hope to portray HD’s devastating impact and the urgent need for effective treatment.

In the HD world, scientists avoid the word “cure.” HD is so complex that many have said a cocktail of drugs will be needed to target the multiple problems in the brain and elsewhere in the body.

For the first time, actually switching off or completely removing a mutation might enable us to imagine the way to a cure.

Gene Veritas (aka Kenneth P. Serbin) (photo by Yi Sun, Ph.D.)

Ionis Phase I Huntington’s disease trial at halfway mark: ‘No surprises so far’ means good news

At its halfway mark, Ionis Pharmaceuticals' historic Huntington’s disease Phase 1 gene-silencing clinical trial is on track to finish as scheduled in late 2017, company officials said in an interview on September 26.

“What we can say is that the trial is going well,” said Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for the company’s neurology programs.

Dr. Bennett added that no “issues” have arisen so far in the Phase 1 safety and tolerability study of its drug IONIS-HTT_Rx in patients with early HD. IONIS-HTT_Rx aims to reduce the production of huntingtin protein in brain cells. This approach, if it advances to Phases 2 and 3, may have the potential to slow, halt or perhaps even reverse the progression of HD symptoms. The trial began in September 2015, with participants in England, Germany, and Canada.

The Ionis HD team explained that the Phase 1 trial is not assessing the drug’s efficacy. Each patient in the trial receives the drug for just three months – not long enough to gauge any impact on symptoms.

Furthermore, the trial is “double-blinded”: trial participants, trial administrators, and Ionis scientists do not know who is getting the drug or a placebo. This insures that bias and other external factors don’t affect the trial results.

Nevertheless, the absence of problems is good news.

No surprises have occurred to date, commented Anne Smith, Ph.D., the Ionis director of clinical development and the individual responsible for the day-to-day management of the trial.

“It’s blissfully quiet,” Dr. Smith said. “You don’t want surprises in clinical trials. Most surprises in safety trials are bad surprises. This one is surprise-free to date.”

Also, trial participants had no difficulties with the delivery of the drug via injections into the spine (so-called intrathecal injections), added Roger Lane, M.D., the Ionis vice president for neurology clinical development and one of the designers of the trial.

Watch my reaction after the interview at Ionis headquarters on September 27 in the video below.

Ionis Phase I HD Trial at Halfway Mark: 'No Surprises So Far' Means Good News from Gene Veritas on Vimeo.

Phase 2 could start in 2018

“We’re continuing to enroll patients in the study,” Dr. Bennett said. A total of 36 patients divided into four cohorts – each subsequent cohort taking a higher dose of IONIS-HTT_Rx – will participate in the trial.

Ed Wild, M.D., Ph.D., one of the administrators of the trial at University College London, announced in June at the annual convention of the Huntington’s Disease Society of America in Baltimore that the third cohort had received permission to receive the drug. (Click here to watch a video of Dr. Wild’s presentation.)

“This is a new therapy, and we want to make sure that we’re doing no harm,” Dr. Bennett emphasized. “Everything is geared towards the safety of the drug at this stage.”

If Phase 1 confirms safety and tolerability, a year-long Phase 2 trial to measure efficacy in a larger number of patients likely would start in 2018, Dr. Bennett said.

Infants on an Ionis SMA drug living longer

The update provided by the Ionis HD team came in the wake of further validation of the company’s scientific approach.

Ionis makes antisense oligonucleotides (ASOs, artificial strands of DNA) that alter the expression of genes and can therefore potentially serve as treatments for genetic diseases. On August 1, Ionis and its partner Biogen actually halted a Phase 3 trial of an Ionis ASO (nusinersen) in infants with spinal muscular atrophy (SMA) because the drug, which increases the level of a key protein, was working so well.

On September 27, Biogen announced that it had completed its application for priority review of nusinersen by the U.S. Food and Drug Administration (FDA).

Like HD, SMA is a genetic neurodegenerative disorder. It primarily affects children, who “end up becoming paralyzed over time,” Dr. Bennett explained, and become vulnerable to respiratory infections or other diseases. Children diagnosed with the most severe form of SMA generally live less than a year, he said. In a less severe form of SMA, children lose the ability to walk over time as they grow up, Dr. Bennett added.

“I think the surprising thing that we found – and this was evidence early in the program – was that we didn’t just stop the decline in these patients, but we actually reversed it,” Dr. Bennett said. “That was really unexpected. I should say that they’re not cured of the disease, but they’re doing much better now than expected. They are surviving longer based on the natural history of the disease.”

These results demonstrated the body’s capacity to mend once the cause of a disorder is removed, he observed.

“We’re hopeful that will also occur in Huntington’s,” Dr. Bennett affirmed. “We have to demonstrate it, but I think there’s a precedent now in these neurodegenerative diseases. If you remove the insult or the toxicity, you can recover function.”

Dr. Frank Bennett of Ionis makes a point during discussion of the company's Phase 1 clinical trial for a Huntington's disease treatment (photo by Kristina Bowyer, Ionis)

Preparing for the HD clinical study

In the Phase 1 IONIS-HTT_Rx trial, clinical trial investigators are collecting some information about the drug’s effect on biomarkers (indicators of a disease mechanism or drug impact) that may help the team design a potential Phase 2.

According to Dr. Lane, before a patient receives each of the four planned doses, the trial administrators collect samples of cerebrospinal fluid (CSF) that will be used to measure levels of huntingtin protein and a variety of other protein markers of neuronal injury and inflammation. Patients also undergo brain scans to look at the volumes of, and the connectivity between, different parts of the brain that are known to be affected in HD.

Another biomarker is neurofilament, described by Dr. Bennett as a protein involved in the cytoskeleton or internal “scaffold” of neurons.  “It’s something very specific to neurons,” said Holly Kordasiewicz, Ph.D., the Ionis director of neuroscience drug discovery, who participated in selecting the ASO, researched it in animals, and is developing biomarker tests for the Phase 1 study. “When the neurons are damaged, neurofilament is released. In a number of neurodegenerative diseases, neurons are dying and neurofilament levels go up.”

In HD, brain cells die. In a clinical study, a decrease in neurofilament would suggest that the drug is protecting neurons, Dr. Kordasiewicz added.

Ionis Huntington's disease clinical trial planners Dr. Anne Smith (left), Dr. Roger Lane, and Dr. Holly Kordasiewicz meet with Gene Veritas (in green shirt) on September 26, 2016, to provide an update on the company's Phase 1 HD trial (photo by Kristina Bowyer of Ionis)

Getting the design of Phase 2 right

The participants in the IONIS-HTT_Rx study undergo a battery of tests that assess memory, thinking, movement, behavior problems, and abilities to perform every-day activities. This is in preparation for use of such measures in a potential Phase 2.

“We’re trying to get the information to design the best efficacy study that we can,” said Dr. Kordasiewicz. “A really sad outcome would be failure of an efficacy study due to the wrong design, not because the drug’s not working. You have to be sure you’re picking the right dose and the right endpoints for the efficacy study.  That’s why all the extra stuff goes into these Phase 1 trials, so that you can get the design right and have the best shot at giving the drug the best chance at working.”

The large burden of work on patients and trial administrators in Phase 1will ultimately allow Ionis (and its partner Roche) to “simplify” potential Phase 2 and 3 trials, making them quicker and making it easier for patients to participate, Dr. Bennett added.

Seeking answers to key questions

This is the first time that an HD gene-silencing drug is going into the human brain. In animals such as mice and non-human primates, the drug gets into both the cortex (the outer, main part of the brain, linked to consciousness) and the striatum (a part of the brain deep under the surface that is involved in movement). Both areas are affected by HD.

A key question for researchers: must IONIS-HTT_Rx reach the striatum to help alleviate HD?

According to Dr. Kordasiewicz, the latest research in HD mice (conducted by William Yang, M.D., Ph.D., of the University of California, Los Angeles) demonstrates that silencing the huntingtin gene in the cortex was more effective than silencing the gene in the striatum, but that silencing in both cortex and striatum was the most effective approach.

Another concern of scientists and HD patients and their families involves the abilities of the ASO, or gene-silencing drug. Should the ASO be designed to reduce only the so-called “bad,”mutant huntingtin? Or is it okay to reduce both the bad and the normal version, which is inherited from the unaffected parent? The IONIS ASO is expected to do the latter.

According to the Ionis HD team, the controversy over this question is diminishing. Studies in animals support the safety of approaches that reduce both mutant and normal huntingtin.  Additionally, Dr. Guohao Wang’s work in mice showed that eliminating huntingtin completely in later life did not have any adverse consequences.

“That was good evidence to support our approach,” said Dr. Lane.

Involving the U.S., thanking patients and families

Many in the HD community have asked: why didn’t Ionis conduct Phase 1 in the United States? And would a potential Phase 2 include Americans?

“I’d be surprised if the U.S. wasn’t involved in a Phase 2 study, as well as additional countries, but I don’t think we are in a position to say specifically which countries are going to be involved,” Dr. Bennett commented. “There were strategic decisions that caused us to go to Europe and Canada first. It’s not that we want to ignore the U.S.” He explained that it was faster to start a trial in Canada and Europe.

The Ionis HD team thanked the Phase 1 participants and their families for their involvement in the Phase 1 study.

“It’s been a very good community and very supportive of our efforts,” said Dr. Bennett. “We also want to thank them for their patience.”

(Disclosure: I hold a symbolic amount of Ionis shares.)

(Click on the links below for past coverage of the Ionis HD project.)

Chief Huntington's disease drug hunter: 'every confidence first treatments' in the works

Huntington's disease patients get first dosing in historic Isis Pharmaceuticals' gene-silencing drug trial

Isis Pharmaceuticals launches historic clinical trial to silence Huntington's disease gene

Moving toward a potential treatment: Isis, CHDI researchers outline upcoming Huntington's disease gene-silencing trial

A key new ally in the search for Huntington's disease treatments

Quickening the pace towards a Huntington's disease gene-silencing clinical trial: pharma giant Roche, Isis enter partnership

Designing the best drug possible to defeat Huntington's disease

Building a 'laser-guided missile' to attack Huntington's disease

Observing the cure in progress 

Do we need to shock the world to strengthen the Huntington’s disease cause?

May is Huntington’s Disease Awareness Month. During this time, we in the HD community make a special effort to educate the public and our leaders about the untreatable, fatal genetic disorder that affects thousands of American families.

It’s also a time to reflect on the very meaning of awareness and how we build it.

In our media-saturated world, people often equate awareness with media exposure.

However, from my standpoint as an activist who has worked at all levels of the movement – from local volunteering to statewide stem-cell advocacy to global networking for the upcoming World Congress on Huntington’s Disease – I view the quest for media exposure as a necessary but hardly sufficient condition for awareness-building.

Disease and the public eye

Some recent news items highlight the importance of media exposure, its connection to awareness, and the potential drawbacks of over-emphasizing exposure.

The revelation by actress Angelina Jolie that she had undergone a preventive double mastectomy after testing positive for a breast cancer gene led a sufferer of a lesser-known disease, dystonia, to publish a commentary on the difficulties of building support for research for her condition.

“If I told you what my issue was, you would probably shrug and reply that you’d never heard of it,” wrote Allison Hersh London, the chairwoman of the Young Leadership Council at the Bachmann-Strauss Dystonia and Parkinson Foundation, in an article titled “Disease and the Public Eye” in the May 18 edition of the New York Times. “There aren’t any public service announcements about it or telethons. No Angelina Jolies to bravely inform the world. Just people like me, in supermarket checkout lines.

A movement disorder, dystonia causes involuntary muscle contractions resulting in twisting and repetitive movements.

“And this, I realize, is at the core of a problem that extends beyond me and my condition and that affects the way all of us respond to illnesses, some of which are the subject of public attention — and resources — and some of which are not.”

Sound familiar? It’s what the HD community said for decades. The only famous American to die of HD, Woody Guthrie, left us almost 50 years ago.

But now read what London says about HD:

“It’s odd to find yourself envying people who have diseases that get more attention than yours,” she wrote. “But I can’t help it. Dystonia is quite rare but, by some estimates, there are more people who have it than have Huntington’s disease, A.L.S. and muscular dystrophy combined. So the simple prevalence of an illness doesn’t explain why some illnesses are better known and better studied than others.”

Although recognizing that dystonia isn’t neurodegenerative or fatal, London uses the very same tactic of comparing disease numbers that some of us in the HD community – including myself – have used to justify more attention and research dollars for our disease.

What’s odd for me as an HD advocate is to see Huntington’s referred to in this manner. Despite HD’s occasional presence in the news and entertainment media over the past five decades, most people in the supermarket line still would say: “never heard of it.”

HD people do know about dystonia, however. In fact, before my mother was tested for HD in 1995, one doctor first thought she had that disorder. In addition, many HD patients do have dystonia as a symptom.

Citing a research study called the “Katie Couric Effect,” London affirms that a celebrity connection to a disease “can have a substantial impact on what the public does.”

London repeats what we’ve all heard: “Awareness generates funding, and funding generates research, which can lead to enormous life-changing differences for people who struggle with illnesses you probably haven’t heard of.”

Nevertheless, she concludes, “what’s most important is telling people about the disease” on an individual level.

‘I Wish My Son Had Cancer’

In England, Alex Smith, a father fighting to save his son Harrison from the fatal condition known as Duchenne muscular dystrophy, took out an ad in London’s Evening Standard.

The ad photo (above) could just as easily represent a parent from an HD family, like the one I took at last year’s HDSA national convention of little Kayden Bujnowski, at risk for developing juvenile HD, her HD-afflicted mother Heather Lewis, and her father Jason Bujnowski (see below).

However, in the case of Harrison, the parents and the ad agency headlined their ad with the words “I Wish My Son Had Cancer.”

“Harrison, my 6 year old, has Duchenne Muscular Dystrophy,” the ad states. “He’s one of 2,500 sufferers in the UK who’ll die from it, most before they’re twenty. Unlike cancer, there’s no cure and no treatment. And because you’ve never heard of it, very little funding either.”

"So far, the finished ad has received considerable support among other parents of children with Duchenne," journalist Meg Carter wrote about the ad, noting that people from far away as Brazil have donated a total running into the thousands of British pounds towards research for treatments. "However, some online comment on the charity's Facebook page has questioned the merit of, in effect, setting up different childhood illnesses in competition for donors' support."

As I wrote about Jolie’s preventive operation, people in the HD community would jump at the opportunity to reduce their level of risk for a disease that is 100% genetic and eventually strikes every carrier of the gene.

Indeed, we are desperate for treatments.

However, I cannot recall any instance in which a family or HD organization went to such extremes to generate publicity and funds.

Many forms of awareness-building

In seeking media exposure, we in the HD and other disease movements attribute to it an almost magical power to solve all of our problems and instantly bring the cure.

In the process, we can lose sight of the many other, equally important forms of awareness-building.

Practically everything we do in the fight against HD involves awareness-building: the doctor-patient relationship, informing people in our workplaces and community, and advocating in the public arena for such issues as stem cell research and passage of the Huntington’s Disease Parity Act.

Awareness-building requires relationship-building.

All of this is hard work. And it lacks the glamour of the fifteen minutes of TV fame or a 700-word newspaper op-ed piece.

Self-awareness first

The most important form of awareness-building takes place in our families and at the level of the individual affected by HD.

Because of the fearful symptoms and deep stigma associated with HD, so many of us hide in the terrible and lonely “Huntington’s closet.” The first step in awareness is to exit that closet and strive to build a family conversation about HD.

In our rapidly advancing biotechnological era, in which scientists have solved many of the mysteries of HD and opened the way to potential treatments, awareness-building also means confronting challenges such as genetic testing and grasping why it’s significant that we join research studies and clinical trials for defeating the disease.

It all begins with each of us. In building self-awareness with respect to HD, we can take the next big step of talking to a relative, joining a support group, visiting an HD clinic, and, when the moment is right, sharing our stories in the way that so many HD families do in the daily e-mail features of the Huntington’s Disease Society of America (HSDA) in May.

Deep pockets and working behind the scenes

It’s understandable that people with dystonia, Duchenne’s, or Huntington’s want to persuade or even shock the public into supporting their cause.

However, most of the process of fighting a disease takes place in physicians’ clinics and scientists’ labs. In America, a vast biomedical and pharmaceutical system discovers, produces, markets, and administers treatments. The politics and finances behind this system operate far from the public eye and, usually, media scrutiny.

In the fight against Huntington’s disease, the dogged determination and leadership of individuals such as Marjorie Guthrie, Woody’s widow and the founder of HDSA, and the Wexler family of the Hereditary Disease Foundation proved crucial in building both the public and self-awareness of the HD community and paving the way to key discoveries that have brought the hope of treatments.

Since 2003, however, the leadership in HD therapeutic research has come largely from the CHDI Foundation, Inc. Backed by a group of anonymous donors, CHDI spends tens of millions of dollars annually to fund drug-discovery projects. It also holds highly technical conferences to discuss the worldwide efforts to find treatments.

CHDI works without celebrities. While it has made waves in the world of science, it quietly goes about its work towards one goal – stopping Huntington’s disease – albeit HDSA shoulders the responsibility of advocacy, awareness, and services to HD families.

In the context of our biomedical system, CHDI illustrates a key point: having deep pockets and working behind the scenes can play as large a role – if not greater – in combatting a disease as public awareness.

HD scientists do find inspiration in the stories of HD patients.

However, they are also motivated by the deep curiosity characteristic of science researchers. HD provides a daunting challenge, one that has attracted some of the best scientific minds of our era. Additionally, it serves as a model for studying other genetic and neurological conditions, and the tools and techniques used in HD research can be applied to other scientific questions.

The momentum of science means that diseases even rarer than HD are benefitting from increased research and funding, as pointed out by Carl Zimmer in an article on fibrodysplasia ossificans progressiva, a genetic disorder that disables people by causing them to grow extra bones, in the June 2013 issue of The Atlantic. HD affects an estimated 1 in 10,000, the bone disorder 1 in 2 million!

“The medical establishment itself has shifted its approach to rare diseases, figuring out ways to fund research despite the inherently limited audience,” Zimmer observed. “Although rare diseases are still among the worst diagnoses to receive, it would not be a stretch to say there’s never been a better time to have one.”

In discovering a drug for a disease like HD, many important parts of the story will emerge only years later. Some aspects may never reach the public arena.

What counts most is stopping the disease.

Pope Benedict XVI’s resignation: a witness to aging, a signal for a new bioethics

Undoubtedly, history will most remember Pope Benedict XVI not for any accomplishment or lack thereof, but for his courageous and humble decision to become the first head of the Roman Catholic Church to abdicate in seven centuries – and only the fifth in 2,000 years of Catholicism.

One cannot fail to be moved by the 85-year-old leader’s recognition that he no longer possesses sufficient “strength of mind and body,” leaving him unable “to adequately fulfill the ministry entrusted to me.”

He made the announcement on February 11. He will leave his post on February 28. Shortly thereafter, a conclave of cardinals, the top leaders of the Church, will meet to select a new pope from among themselves.

Benedict XVI’s resignation is a witness to aging and human mortality.

No matter what our beliefs about religion, this simple but profound action gives us pause to reflect on how we can accept our own human limitations.

For the Huntington’s disease community, it also provides an opportunity to recall the ethical, social, and spiritual dimensions of our collective struggle.

Turning over the keys

In a world with many governments and institutions ruled by old men unwilling to release their grip on power, Benedict XVI has voluntarily relinquished control of the Church – the epitome of male dominance – to go live in a building that has until now served as a cloistered convent.

Pope Benedict XVI 

In a global, image-conscious youth culture offering plastic surgery and hair implants to the middle-aged and elderly, Benedict XVI has said that it’s okay to age.

Many elderly people resist giving up freedoms such as the pleasurable and powerful experience of driving a car until an adult child worried about safety takes away the keys or gets a court order to declare the parent incompetent.

Benedict has turned in the keys on his own, saving others from potentially embarrassing and even dangerous predicaments and opening the door to potentially more youthful leadership in greater tune with today’s world.

According to the New Testament of The Bible, Jesus gave the Apostle Peter the keys to the Kingdom of Heaven. The historical successor to Peter, Benedict XVI will pass on those spiritual keys to a new pope, another illustration of the profound humility of his abdication.

Each day, HD-affected people and their caregivers strive together to strike a balance between the individual patient’s desires and the need for proper care. We, too, face the terrible burden of wondering about the right moment for the caregiver to take over the keys.

Gene-positive, asymptomatic people like me and those with early symptoms wonder how long we can hold onto our keys, and we worry greatly about burdening our families.

Ultimately, those keys represent our lives and our hopes for a peaceful death and the possibility of a hereafter – a place without the suffering of Huntington's disease.

Revealing frailty

Rather than leave the world the spectacle of a pope struggling to hold onto the reins of power while ensconced in the palatial papal dwellings, Benedict XVI may instead ultimately provide the world the image of a retired pope hospitalized or sheltered in what could effectively become a nursing home, with caregivers assisting him with basic needs.

If Benedict XVI develops or already has Alzheimer’s or some other neurodegenerative disorder, rather than be hidden behind a Vatican bureaucracy nervous about a transition of power and the Church’s image, his condition will become known to the world.

His predecessor, Pope John Paul II, suffered from Parkinson’s disease. Despite his symptoms, John Paul II kept up his busy schedule of trips and public appearances. He also advocated for greater research towards a cure.

The HD community has long understood the similarities between the frailties caused by Huntington’s and those of Alzheimer’s, Parkinson’s, and other disorders. We can stand with Benedict XVI as he faces the possibility of his own neurodegenerative symptoms, and we will continue to advocate for remedies for HD, still untreatable but the focus of intense research efforts.

Revising bioethics

The social impact of Huntington’s disease and the efforts to understand and treat it have thrust our community into the forefront of the biotechnological revolution.

As I recently wrote, “The story of Huntington's is the story of our time. Huntington's was one of the very first diseases for which a genetic test was developed. As knowledge increases about numerous other health risks, medical ethics must undergo profound revision, and a genetic-rights movement must arise. To borrow one scholar's phrase, disease-gene carriers like me are ‘moral pioneers’ on the genetic frontier.”

Benedict XVI’s witness to aging and mortality comes at a time when the Church hierarchy, Catholic believers, and society in general have struggled mightily with other life-and-death issues such as birth control, abortion, embryonic stem cell research, and mercy killing.

Benedict XVI shored up traditional Church teachings on these matters, but he also belonged to a generation of Church thinkers faced with the challenge of formulating a system of Catholic bioethics to meet both the ever-expanding promise and dangers of the biotechnological era.

Thus, Benedict’s witness to aging could help the Church forge ahead with a carefully conceived and balanced bioethics.

By suddenly opening up the Church to the selection of a new pope, Benedict XVI has created potential space for new ideas regarding bioethics.

If a pope can humbly resign, perhaps the Church can humbly admit the need for greater flexibility.

Responding to challenges

Pope John XXIII (1881-1963, pontiff 1958-1963), a simple man of peasant origins not expected to make waves, surprised the world in 1959 by calling the Second Vatican Council, which took place from 1962-1965. This June 3 marks the 50^th anniversary of John XXIII’s death.

Vatican II brought the Church into the modern world by carrying out the most sweeping reforms in the history of Catholicism. Those reforms included the end of the universal Latin Mass (in favor of the Liturgy in local languages), initiation of dialogue with other religions as well as with antagonistic political creeds such as Marxism, and greater participation by laypersons in the Mass and administration of the Church.

Vatican II responded to a great malaise in the Church in the 1950s caused by censorship of innovative ideas and an exaggerated dependence on tradition and ecclesiastical authoritarianism. Today a similar malaise – created by the current sex-abuse scandals and cover-ups involving priests, bishops, and even cardinals – plagues the Church.

In the late 1960s, powered by the energy of Vatican II, the Church seemed on the rebound.

Future reforms

As is well known, Benedict XVI worked hard to contain and even reverse the trends unleashed by Vatican II.

However, unlike the 1960s, when so much seemed possible for the Church, today the institution suffers from a crisis of credibility.

Liberal Catholics like me have again begun to urge that the Church call for a Vatican III to address such issues as the sex-abuse scandal and the ordination of women (for another example, click here). The Church also needs reform on issues such as obligatory priestly celibacy, the ordination of married men, and hypocrisy about homosexuality in an institution with large numbers of mainly closeted gay clergy.

A Vatican III was virtually impossible under Benedict XVI as active pope. However, his radical departure into retirement has now made a council possible. It may not matter if the new pope is another conservative, because Benedict XVI’s powerfully symbolic resignation, his witness to aging, has signaled to the leadership that it can and should explore new avenues, new modes of action.

Bioethics could and should become the centerpiece of a Vatican III.

As the Church clamored for peace and social justice in the 1960s, today it can take a new and invigorating leadership role in helping the world adapt to the challenges of the genome, the environment, new forms of human relationship, and the immense caregiving burden created by science and medicine’s ability to prolong the life of the body ahead of the mind.

In its long and often wise history the Church has evolved gradually and deliberately. It can now begin to embrace the postmodern world.

We in the HD have also born witness – to immense suffering, to an ambitious scientific effort to improve the lives of people through the search for treatments and cures, and to hope. We have much of our own wisdom to offer the Catholic Church, and the world, in the quest for a new bioethics.

(A similar version of this article appeared today in Portuguese in the Brazilian newspaper O Estado de S. Paulo.)

California stem cell agency approves $19 million clinical trial project as Huntington’s disease families ‘change the course of science’

Adult stem cells designed to rescue brain cells from death in Huntington’s disease patients could enter human testing in the next three to four years, thanks to a $19 million grant to an HD research team at the University of California, Davis (UC Davis), from the California Institute for Regenerative Medicine (CIRM).

If successful, this first-ever stem cell clinical trial for Huntington’s could pave the way for a possible treatment of the devastating disorder.

At a public meeting July 26, the oversight board of the $3 billion stem cell agency announced the award to the lab of researcher Jan Nolta, Ph.D., a recognized specialist in mesenchymal (pronounced “meh-zen-KI-mal”) stem cells (MSC), and her collaborator Vicki Wheelock, M.D., a neurologist and the director of the Huntington’s Disease Society of America’s Center for Excellence for Family Services and Research at UC Davis.

Dr. Nolta aims to introduce MSCs, which act as natural “paramedics” in the body, into the brains of symptomatic HD patients to test for safety and tolerability. The trial doses will be made from a sample of MSCs extracted from a healthy donor.

MSCs produce a so-called “fertilizer for the brain” (BDNF, brain-derived neurotrophic factor), whose levels plummet drastically when someone has HD. Dr. Nolta and her team have engineered MSCs to produce higher levels of BDNF in an attempt to help HD-damaged neurons recover and avoid death, thus slowing, halting, or perhaps even reversing the course of HD.

Dr. Nolta’s collaborator Gary Dunbar, Ph.D., of Central Michigan University, has already demonstrated that these MSCs mostly stop symptoms in transgenic mice that have been given the abnormal HD gene.

Dr. Jan Nolta (above) at the HD work bench at the Institute for Regenerative Cures. Below, Dr. Vicki Wheelock (photos by Gene Veritas).

The Nolta-Wheelock grant was one of eight CIRM grants totaling $151 million to labs seeking treatments for debilitating or fatal diseases, including Lou Gehrig’s disease, cancer, heart disease, and spinal cord injuries. The awards were the second largest research round in CIRM history. In 2009 the agency granted more than $200 million to researchers.

With a score of 87/100, the Nolta-Wheelock grant ranked highest in the state.

“We’re just so glad that we didn’t let the community down,” Dr. Nolta told HD activist Melissa Biliardi on The HD View internet radio program on July 23 in anticipation of the expected award.

In this same round UC Davis received two other grants – to seek treatments for peripheral artery disease and osteoporosis – that Dr. Nolta will help oversee in her role as the director of the UC Davis stem cell program and the university’s Institute for Regenerative Cures (IRC), which has nearly 150 affiliated faculty researchers.

“People are hopeful, truly hopeful for the first time,” Judy Roberson, the former president of the Northern California Chapter of the Huntington’s Disease Society of America (HDSA) and the widow of an HD victim, said after the CIRM announcement. “This is a nightmarish, cruel disease in every way but now, thanks to CIRM, we are turning the dream of a stem cell therapy trial into a reality. Research means hope for people with this disease, but research costs money. CIRM has given us all hope.”

The trial’s proposed timeline

CIRM will grant the $19 million over four years, the proposed timeline of the clinical trial project. Most of the money will cover charges such as surgeries, operating room and hospital costs, MRI scans, and other items related to the actual trial.

According to the proposal, the UC Davis team will spend the first year testing the safety of MSCs in healthy non-human primates. This stage of the project will help the team secure the necessary approval for human testing from the U.S. Food and Drug Administration (FDA), which regulates clinical trials.

In the project’s second year the team hopes to enroll at least 26 early-stage HD patients in an observational study, including motor and psychiatric tests and MRI brain scans, to obtain basic measurements of their health for comparison with readings to be taken during the clinical trial.

At the start of the third year, if all regulatory approvals have been obtained as planned, the patients will receive a single, direct injection of the MSCs into each side of their brains (a bilateral intrastriatal injection). A special neurosurgical team, which will include experts from the University of California, San Francisco, will bore a tiny hole into the skull to insert a tiny cathether to deliver the cells. Direct insertion is necessary because of the blood/brain barrier, which allows few medications to enter the brain. Patients will have part of their heads shaved. However, their hair should grow back, and the holes will heal over.

Half of the patients will receive MSCs with the extra BDNF-producing capability, while the other half will receive a placebo, MSCs without that capability.

Trial participants will receive dosages in groups and on a staggered schedule, with each successive group receiving a higher amount of the MSCs.

The remainder of the trial will primarily check for the safety of the MSCs. As a secondary goal, the scientists and physicians will also look for alleviation of symptoms and evidence that the MSCs are improving the health of the brain.

This first step in the trial is known as Phase I. If the MSCs prove safe, the team would seek funding for Phases II and III to fully measure the cells’ efficacy.

All of these plans must receive formal approval from UC Davis’s internal review board and then the FDA, after which full details will become available for potential trial participants.

A brief history of stem cells

To understand Dr. Nolta’s work we must travel back in time to explore the roots of today’s revolution in stem cell research.

Stem cells became a hot topic in the first decade of the 21st century because of the controversy over one type: embryonic stem cells. However, stem cell research long predates this controversy.

Recall that a stem cell has a very important property: it can make cells that eventually become another type of cell such as a muscle cell, skin cell, or brain cell (neuron).

Stem cells help our bodies regenerate lost or worn tissue and components such as our blood, liver, and skin.

Humans have understood the idea of regeneration since ancient times, and scientists first started discussing the concept of stem cells in the mid-1800s. Scientists first discovered stem cells in mice bone marrow in the early 1960s.

The very first stem cell therapy (treatment) in humans took place in 1968 with the successful bone marrow transplant for a leukemia patient whose marrow donor was an identical twin. This type of transplant helps the patient because bone marrow contains stem cells that produce new blood cells. Because of stem cell research, other kinds of transplantation and tissue regeneration have become possible.

Over the last few decades, scientists have identified other types of stem cells, including those that produce neurons. Stem cell research is now burgeoning around the world. Scientists use stem cells both to understand human biology and to seek therapies for diseases and traumas.

In August 2001, President George W. Bush stopped federal funding for new embryonic stem cell research because of his belief, shared by a good number of Americans, that such research destroyed human life (the embryo from which the stem cells were taken) and was therefore immoral. In California Bush’s restrictions spurred a successful movement to pass a 2004 ballot initiative, Proposition 71, that skirted the president’s order with state-level funding, created CIRM, and catapulted the state into global leadership in stem cell research.

In recent years, however, new discoveries have lessened the controversy about stem cells. Scientists have made many advances using adult stem cells – those extracted from a living human being without any risk. In 2006 researchers achieved another milestone that reduced the need for embryonic stem cells: they could now take cells from the skin or other parts of the body and reprogram them into a stem cell.

Dr. Alvin King of the University of California, Irvine, displays a neural stem cell on the screen of a microscope (photo by Gene Veritas).

The MSCs, Dr. Nolta’s focus for the past 25 years, are adult stem cells. Everyone has MSCs. They are found in the bone marrow, as well as in fat, dental tissue, and the umbilical cord. They can make bone, tendons, ligaments, and other connective tissues. MSCs grow well in lab conditions, making them a prime candidate for research.

Along with other scientists, in recent years Dr. Nolta and Leslie Thompson, Ph.D., of the University of California, Irvine, another CIRM grantee, began employing stem cells in Huntington’s research. Besides MSCs, HD researchers use human embryonic stem cells, human induced pluripotent stem cells, neural stem cells, and others.

In Dr. Nolta’s assessment, MSCs appear to have especially great potential in treating HD because of their abilities as the body’s “paramedics.” This potential is described in detail below.

From child scientist to MSC expert

Dr. Nolta’s path to the potentially historic MSC HD clinical trial began in childhood and took shape in the midst of the stem cell revolution.

“I think I was probably born a scientist,” she told me during a May 2011 visit to her lab on the occasion of the HDSA Northern California Chapter’s annual convention. “I was the kid that was out in the yard investigating bugs and watching eggs hatch and feeding baby animals that were rescued and trying to understand how caterpillars went through the chrysalis form and came out as moths and butterflies.”

Raised by a single working mom in the small northern California town of Willows and depending on grants and waitressing for her college education, Dr. Nolta received a degree in biology from Sacramento State University in 1984.

After graduation Dr. Nolta took M.A.-level science courses at UC Davis and volunteered in a lab. “We could take stem cells from the bone marrow and culture them,” she recalled. “There was this ‘magical’ potion that we could put them in and culture them for just a few days and could watch them divide and grow into blood cells. I wanted to secretly keep the cultures growing and study them.

“Where I fell in love with mesenchymal stem cells was in 1987. We started doing long-term bone marrow cultures, and there’s a component that grows out when you take a marrow aspirate from a human being that’s a mono-layer of broad, flat cells.  We used to call those the marrow-stromal cells. They later got renamed to mesenchymal stem cells due to their potentiality and all that they can do.”

Dr. Nolta learned that MSCs could assist greatly in gene therapy. Also known as cellular therapy, gene therapy involves the use or alteration of genes to treat disease. Dr. Nolta was impressed with MSCs’ strong ability to assimilate and deliver gene therapy products.

“I realized very quickly that we could engineer them to even better support the other cells in the body,” she explained.

To deepen her knowledge of stem cells and MSCs, Dr. Nolta enrolled in the Ph.D. program in molecular microbiology at the University of Southern California under the mentorship of Dr. Donald Kohn, a specialist in pediatric bone marrow transplantation. At Children’s Hospital Los Angeles she assisted in his pioneering work on bubble baby syndrome, AIDS, and other conditions.

From this experience Dr. Nolta learned the techniques of gene therapy, growing stem cells, and applying stem cell therapies in the clinic. With Dr. Kohn’s team, she performed the first cord blood gene therapy trial for infants born with bubble baby syndrome, a type of serious immune deficiency.

In 2002 the Washington University School of Medicine in St. Louis, one of the nation’s top medical schools, recruited Dr. Nolta to help build its programs in gene therapy and stem cell research. There she continued her work on gene therapy and MSCs and collaborated with her close colleague Gerhard Bauer, Ph.D., in the establishment of a GMP (good manufacturing practice) facility, a highly advanced lab crucial for producing cell and gene therapies.

The power of grassroots advocacy

However, the future of stem cell research lay in California. In 2007 UC Davis lured Dr. Nolta back to her home state to direct its stem cell programs under the umbrella of the brand-new IRC, the Institute for Regenerative Cures. CIRM awarded UC Davis $21 million to construct the IRC and its state-of-the art GMP facility. UC Davis contributed $40 million to the project.

With little knowledge of Huntington’s disease, Dr. Nolta had no plans to include it in her research program at the IRC when she was recruited.

Around the state, however, HD advocates were telling their stories of the desperate need for treatments at the public hearings of the CIRM oversight board. They pushed hard for the CIRM to back HD research.

UC Davis stem cell program manager Geralyn Annett (left), HD patient Sharon Shaffer, Alexa Shaffer,  and Dr. Nolta advocating for HD research at a CIRM board meeting at UC San Diego in 2008 (photo by Gene Veritas)

During her recruitment trip to UC Davis, Dr. Nolta met Dr. Wheelock of the HDSA Center of Excellence.

“Have you ever considered using stem cells to treat Huntington’s disease?” asked Dr. Wheelock as she rode with Dr. Nolta in an elevator.

“You know, for the last 20 years, I have been researching how to use stem cells to treat every part of the body except the brain,” Dr. Nolta responded, citing the critical hurdle of the blood/brain barrier.

“The families impacted by Huntington’s disease are truly remarkable,” Dr. Wheelock rejoined. “I’d love to introduce you to them.”

That conversation spurred Dr. Nolta to take a scientific interest in HD. More importantly, meeting the families deeply moved her. She decided to act.

With initial financial backing from HD advocates from the Sacramento area and elsewhere, Dr. Nolta delved into a project to find a way to use MSCs to combat HD.

Dr. Nolta used her early findings to apply for a grant from CIRM. In 2009 the agency awarded her lab $2.7 million to study the use of genetically reengineered MSCs to block HD at its genetic roots, first in lab dishes, then in mice (explained below).

During our interview at the IRC, Dr. Nolta pointed to the photographs of HD advocates on her desk.

“They change the course of what scientists do,” she said, breaking into tears. “My life was forever changed.”

In all, local fundraising efforts have provided some $100,000 for Dr. Nolta’s work. Donations have included $15,000 from the Deshalamar foundation and $40,000 from Team KJ, an Illinois initiative in support of Kara Jean Fleming, a 40-year-old HD patient. The Joseph P. Roberson Foundation, named for the deceased husband of Judy Roberson, has also supported Dr. Nolta’s work. Many other donors, large and small, have also contributed.

Watching the paramedics in action

With the new $19 million CIRM grant – the largest in Dr. Nolta’s career – she and the UC Davis hope to set their MSC research on the path to a treatment.

The MSCs’ many attributes make them attractive for treating HD.

“They’re very social,” Dr. Nolta explained as she played a highly magnified video in which the MSCs appeared to swim and greet one another like people playing in a swimming pool. “They like to interact with other cells.”

The MSCs also move around the body with great facility, Dr. Nolta added. They can project little tubes, called nanotubules, that tunnel into cells and inject them with necessary items such as proteins and mitochondria, the powerhouses of the cell.

“It’s like giving a cell new batteries,” Dr. Nolta explained. “They just open up a nanotubule and put the new component into the other cell. So that’s why we call them paramedics. It’s like they’re going around with tool kits to repair the other cells…. They like to check out other cells, to see if they’re healthy. They can change what they produce from what they sense from the environment and from the other cells. They just become like little factories.”

“They almost look like living organisms,” I observed.

“They are,” Dr. Nolta said. “They’re alive.”


(Watch the video below to see the MSCs in action.)

Mesenchymal Stem Cells in Action (narrated by Dr. Jan Nolta) from Gene Veritas on Vimeo.

The MSCs’ sociability results in part from the fact that damaged or sick cells and neurons put out “distress signals” that spur the paramedics into action, Dr. Nolta continued.

The same process occurs in the brain, she added. In mice that carry the human Huntington’s gene and have HD-like symptoms, MSCs injected into their brains migrated to the areas of damage.

Transplantations of human tissue often trigger a rejection by the immune systems of the recipients, requiring them to take anti-rejection drugs sometimes for the rest of their lives. This does not occur with MSCs, Dr. Nolta said.

“That’s the beauty of them,” she said. “They’re transplanted from one patient to the next with really no regard to tissue matching. They actually shelter themselves from the immune system through some of the things that they secrete. We think that’s part of their natural function in the body.

“When there’s a wound or a heart attack or some kind of ischemic event, a stroke, they can go to that area, and they want to cause the tissue to heal without scarring. That’s part of their innate mission. They don’t want the immune system to see it while it’s getting fixed up, because you could start making auto-antibodies to that damaged tissue, and then you would destroy that tissue. We think that the MSC just go to the scene of the injury and keep the immune system at bay while they’re doing their remodeling. It’s kind of like keeping everybody out of a construction site.”

The goal: restoring neurons and connections

According to Dr. Nolta, the MSCs secrete substances that help restore the vital connections between neurons. Such connections are lost in HD. Additionally, in secreting BDNF and other brain growth factors, the MSCs can help damaged neurons recover. She likened this scenario to a chain of Christmas lights that, missing a bulb, will go out. Restoring the bulb – a healthy neuron – gets the whole chain working again.

In the case of the proposed clinical trial, the UC Davis team will ramp up the MSCs’ capability to provide BDNF. In mice tests, they have increased that capability by a hundredfold.

The big question, Dr. Nolta told me in an interview on July 30, 2012, is this: how effective will MSCs prove in helping the entire striatum, an area of the brain deeply compromised by HD and where the MSCs will be injected?

“The MSCs can secrete huge amounts of BDNF, so that might be effective” in helping to restore the striatum, she said.

Attacking HD’s genetic roots

If the MSC BDNF trial proves successful, the UC Davis team could use another up-and-coming tool for combatting HD: RNA interference.

In designing a substance known as a small interference RNA molecule (siRNA), other researchers have already reducedthe amount of harmful huntingtin protein in the brains of test animals. A similar approach, known as antisense, has demonstrated similar results.  Both approaches should enter clinical trials within the next few years, if not sooner.

Still in the early stages of this aspect of their research, Dr. Nolta and her UC Davis HD team have discovered a way to deliver siRNA into cells in a dish using MSCs.

Some researchers are examining ways to implant new neurons or fetal-striatal stem cells into patients’ brains to repair the damage caused by HD. However, Dr. Nolta pointed out that those cells could become affected by HD.

The use of siRNA could protect those and other cells from HD. Dr. Nolta has photos and video of the MSC nanotubules transferring siRNA into other cells. Her lab is now testing MSC siRNA in mice.

Controlling the huntingtin gene and protein effectively is the “holy grail” of HD research because it would allow gene-positive, non-symptomatic people like me to take a preventative treatment.

‘A super, super clean place’

Although the human brain has MSCs, in HD people those MSCs make the same mutant huntingtin as the other cells in the brain and, indeed, in the rest of the body. Compromised in this manner, the MSCs in HD people’s brains cannot make necessary levels of BDNF.

As a result, for the Phase I MSC BDNF trial, the HD team will make batches of MSCs from bone marrow cells provided by a healthy donor and therefore containing normal, non-disease-causing huntingtin.

Federal regulations require GMP for any substance that will be tested in humans. Thus, in the run-up to Phase I, the MSC batches will be made at the UC Davis Institute for Regenerative Cure’s GMP facility. It could make enough MSCs for 100 patients, Dr. Nolta said.

“You need your own facility to get up to this scale,” she commented. “How to manufacture these batches of cells is a whole industry in and of itself. It’s usually companies that would do this. Sometimes they charge exorbitant fees.”

This level of “scale-up” to a clinical trial is “our forte here,” Dr. Nolta told me in our recent interview. The National Institutes of Health and insurance companies don’t fund these kinds of initiatives, she noted, leading many drug candidates with good potential to “fall into the valley of death.”

During my visit to the IRC, she referred to the GMP as a “super, super clean place.” It will triple-check the quality of the MSCs.

As explained to me by GMP specialist Bill Gruenloh, normal air contains hundreds of millions of particles per cubic foot. Air handlers and HEPA filters reduce the number of particles in the manufacturing room to only 10,000. Areas under tissue culture hoods have just 100. In addition, the highly specialized GMP employees maintain meticulous records of every article in the facility. A computer constantly monitors the GMP, and the employees double-check readings with hand-held instruments. Thus no micro-organisms are present in critical areas of the GMP.

If a contamination or other problem occurs with a test drug, the GMP records help trace the cause, Gruenloh said. 

UC Davis GMP specialist John Walker at work (photo by Gene Veritas)

The GMP also stores stem cells and other items at carefully controlled, very low temperatures. The UC Davis GMP developed the first GMP-grade cell-sorter in the world, Gruenloh added.

In addition, the GMP houses its own quality control lab to check the safety of products and verify that they are free of contaminants and bacteria.

Putting the project in perspective

As Dr. Nolta has pointed out on several occasions, more than 10,000 patients worldwide have already received MSCs infused into the blood stream. In fact, the drug regulatory agencies of Canada and New Zealand have already approved the use of MSCs to be prescribed as a drug to treat certain diseases, although not yet HD. In addition, at least four companies are currently testing MSCs or MSC-like cells in clinical trials for other neurodegenerative conditions.

As always, we need to recall that only 10 percent of clinical trials ever lead to an actual drug. Mathematically speaking, the odds are stacked against the Nolta-Wheelock project.

Even if the Phase I trial proves a dramatic success, the UC Davis team will need to find ways to fund Phases II and III, which will require larger numbers of participants and thus cost more money. Backed by public bonds, CIRM will run out of money in about four years, unless the agency can attract private investors. At least for now, the state of California’s dire fiscal situation makes further public funding unlikely, although one cannot predict the mood of the voters.

With an eye to the future, Dr. Nolta and UC Davis have secured a patent for the MSC siRNA delivery technology in the hopes that a pharmaceutical firm or other private investor might risk supporting further research and testing in exchange for some of the potential profits from a drug. She noted that companies visit the IRC regularly, although none has yet expressed an interest in supporting HD work.

Despite these caveats, I am struck by the apparent simplicity of the UC Davis approach: using human cells as a way to deliver remedies to the brain.

I am also impressed with the UC Davis team’s boldness in moving as quickly as possible towards a clinical trial. In fact, some scientists think they’re moving too quickly with their siRNA plans, although Dr. Nolta characterized their criticism as a “misunderstanding” of her project, since it is the BDNF trial, not the siRNA, that is moving toward the clinic first. The siRNA studies are only in early rodent testing.

A successful MSC HD trial would extend immense hope to patients suffering from other neurological diseases (such as Alzheimer’s and Parkinson’s), as well as ischemia, heart disease, and other conditions, Dr. Nolta said. Such hope would likely translate into greater private funding for MSC research.

Hope, realism, and future advocacy

California’s HD stem cell advocates – along with fellow HD activists around the world – can feel confident that CIRM is having an important impact on HD research.

We now await the MSC trial results – and with great hope!

However, we should also proceed with patience and realism.

Science takes time.

Furthermore, most scientists think that treating HD successfully will require a cocktail of remedies, not just one.

With grassroots support for, and intense interest in, the UC Davis HD program, the HD community is betting heavily that MSCs will provide a way to alleviate the conditions’ horrific symptoms.

Judging from the unprecedented excitement about the CIRM grant that I have witnessed in the HD Facebook community in comparison with news about other breakthroughs, I think people perceive stem cells as providing the greatest hope. Indeed, for many Americans, stem cells seem to hold an almost magical appeal, as they once did for the young Jan Nolta at the start of her career. People seem to sense viscerally that they can provide cures and replace lost cells and tissues. Could stem cells represent our new Fountain of Youth?

Naturally, we all want, need, and deserve to celebrate the CIRM award.

I myself have advocated for California stem cell research for more than a decade through HDSA-San Diego. Having lost my mother to HD in 2006 at the age of 68 and tested positive for HD in 1999, I anxiously await treatments. When people told me that potential stem cell breakthroughs lay too far in the future to offer me hope, my resolve to fight only strengthened.

Yet we should also keep in mind that scientists are working just as hard on numerous other, highly important approaches. They don’t stir the controversy and publicity that have surrounded stem cells, and many are extremely difficult to understand, but they could very well lead to effective treatments.

In effect, the Nolta-Wheelock project is another “shot on goal” in the search for HD treatments. The CHDI Foundation,Inc., the major private backer of HD drug research, and its collaborators will attempt as many as eight such shots in the next few years. The more shots, the better the chances of finding treatments and a cocktail.

In the meantime, just as Dr. Nolta, the UC Davis team, and scientists around the world work feverishly to liberate us from HD, we in the HD community must continue to strategically advocate for our cause, creatively help change the course of science, and participate in the crucial research studies and clinical trials that provide the key to defeating HD.

* * *

Additional information

Once the UC Davis trial is approved the FDA, details of how to participate will become available at www.clinicaltrials.gov.

For an HD family member’s account of the historic CIRM meeting, read Katie Jackson’s report at The Huntington’s Post.

To learn more about Dr. Nolta’s research, read an article by Dr. Marsha Miller by clicking here.

For the official CIRM evaluation of the project, please click here.

For in-depth reporting on CIRM’s activities, see California Stem Cell Report.

You can also read an impassioned defense of stem cell research by global HD advocate Charles Sabine.

HD scientist Dr. Elena Cattaneo provides an update on the European Union’s support for stem cell research.

For an overview of stem cells, see Stem Cells for Dummies.

On stem cells and HD, also see www.HDBuzz.net.

To see a presentation by Dr. Nolta on MSCs and HD, watch the video below.

Towards Stem-Cell Treatments for Huntington's Disease: Talk by Dr. Jan Nolta from Gene Veritas on Vimeo.